In contrast to several other mental retardation syndromes, the neuropsychology of Down Syndrome is relatively unexplored. The proposed research will fills gap in existing knowledge by testing the functional status of three neural systems particularly at risk in DS: the prefrontal cortex, hippocampus, and cerebellum. We will examine these three neuropsychological domains in a cross-sectional study of two age cohorts of individuals with DS (n=36 each) compared to two control groups, 1) younger normally developing children matched on MA, and 2) CA and MA matched children with non-DS mental retardation. Our component will provide a target phenotype for our colleagues working with mouse models, which will help them isolate the specific genetic determinants of the neural bases of this form of mental retardation.